Case Report Simultaneous Occurrence of Ocular ...downloads.hindawi.com/journals/criid/2014/837625.pdfDisseminated Mucocutaneous, and Multivisceral Involvement of Leishmaniasis

Case ReportSimultaneous Occurrence of Ocular,Disseminated Mucocutaneous, and MultivisceralInvolvement of Leishmaniasis

Cyriac Abby Philips,1 Chetan Ramesh Kalal,1 K. N. Chandan Kumar,1

Chhagan Bihari,2 and Shiv Kumar Sarin1

1 Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India2Department of Pathology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India

Correspondence should be addressed to Cyriac Abby Philips; [email protected]

Received 28 October 2013; Accepted 12 January 2014; Published 18 February 2014

Academic Editors: E. Hadziyannis, J. S. Koskinas, C. Miyabayashi, and T. Tanwandee

Copyright © 2014 Cyriac Abby Philips et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Leishmaniasis is a tropical infection caused by the protozoan, belonging to the group of Leishmania which causes Old World andNew World disease. These are typically divided into cutaneous, mucocutaneous, visceral, viscerotropic, and disseminated disease.Cutaneous leishmaniasis in the presence of visceral disease is a rarity. Isolated case reports have documented this occurrence, in theimmunocompromised setting, and few otherwise. The concurrent presence of visceral leishmaniasis (bone marrow involvement)with solitary cutaneous and ocular disease and also solitary cutaneous and visceral disease (bone marrow involvement) has beenreported before. Here, we present an immunocompetent patient who was diagnosed to have visceral leishmaniasis (liver and bonemarrow involvement) alongwith simultaneous disseminatedmucocutaneous and ocular involvement, a combination that has neverbeen reported before.

1. Introduction

Leishmaniasis, caused by an obligate intramacrophage pro-tozoan parasite, belonging to the group Leishmania, is avector borne disease affecting human population where theparasite, the animal reservoir, and the vector coexist. Sand-flies, belonging to the Phlebotomus species, are the vectorsresponsible for this illness. Leishmaniasis exists in threeforms. The less severe form called cutaneous leishmaniasisaffects the skin, producing characteristic lesions that can bewell managed with treatment. The second form is the moresevere visceral leishmaniasis which affects internal organsand can prove to be fatal if not judiciously treated. A thirdform known as the mucocutaneous leishmaniasis affects skinand mucous membranes of the face, producing ulcerativeand disfiguring lesions [1]. Leishmaniasis is commonly seenin the regions of Nepal, India, Bangladesh, and the MiddleEast. Leishmania is a genus of trypanosomatid protozoa andis spread through bite of sandflies of the genusPhlebotomus in

the Old World and genus Lutzomyia in the New World. Thecutaneous forms of Leishmaniasis are further characterizedinto classical cutaneous leishmaniasis, diffuse cutaneous,leishmaniasis recidivans, and post kala-azar dermal leish-maniasis [2]. The other forms include the classical visceraltype and viscerotropic type. Concurrent occurrence of thesedifferent leishmanial forms in a single host has been reportedvery rarely in literature [3]. The presence of cutaneous andvisceral leishmaniasis has been reported from few countries,mostly in immunocompromised patients. The presence ofdifferent forms of leishmaniasis in an immunocompetenthost has been reported quite rarely.

2. Case Report

A 60-year-old woman, hailing from the eastern state of UttarPradesh in India presented to us with six- week history ofhigh grade continuous fever associated with chills, rigors,anorexia,malaise, joint pains, and severe lethargy.The patient

Hindawi Publishing CorporationCase Reports in Infectious DiseasesVolume 2014, Article ID 837625, 4 pageshttp://dx.doi.org/10.1155/2014/837625

2 Case Reports in Infectious Diseases

also stated that she noticed crops of round, raised lesions thatstarted on her left upper limb, progressing to the right upperlimb and eventually involving the whole face, upper back,and the chest and upper abdominal region, closely associatedwith the febrile episodes. Some of these lesions progressed toincrease in size, becamemore nodular, and developed sunkencenters that drained pus-like material, associated with painand redness. The patient developed jaundice one week pre-ceding her admission to our center whichwas associated withmild to moderate upper quadrant abdominal pain.There wasno history of pruritis, pale-colored stools, or bleeding diathe-sis. The patient also developed swelling of the legs, whichwas nonpainful, not associated with facial puffiness, and notin lieu with decrement in urine output. This was associatedwith painful red eyes and nodular lesions over the eye lidsand in the conjunctiva of the eyes associated with decreasedvision. She is a teetotaler with no known comorbidities in thepast or at the present and has not been consuming over thecounter medications and/or complementary and alternativemedications with/without steroid combinations or on anyother potentially immunosuppressive medications.

On examination, the patient was found to have a tem-perature of 100.8 F. Her blood pressure was 128/88mm ofHg in the right brachial region in supine position and theheart rate was 100 per minute. Pallor was evident; therewas an icteric tinge without clubbing, lymphadenopathy,or cyanosis. There was bilateral pedal, pitting, nontender,and symmetrical edema. The skin examination revealed thepresence of multiple crops of nodular, noduloulcerative,and papular lesions, dispersed throughout the body surface,mostly segregated to the face and upper back. These lesionswere shiny and without skin changes and a few of themshowedpus drainage from the central sunken areas (Figure 1).The eye examination revealed the presence of nodular lesionsover the eyes and conjunctiva associated with conjunctivalsuffusion. The abdominal examination revealed the presenceof hepatosplenomegaly and no free fluid in the abdomen.Therest of the systemic examination was essentially normal.

The blood investigations revealed the presence of hemo-globin of 10.5 g/dL (normal 12 to 15), a total leucocytecount of 5600 per cubic millimeter (normal 4000 to 10000),platelet count of 80000 lakhs per cubic millimeter (1.5 lakhsto 4.5), and an ESR of 80 (normal 0–2) with normocyticnormochromic anemia. Her liver function tests revealed atotal bilirubin of 3.2mg/dL (normal 0.3 to 1.2), of whichthe direct fraction was 1.8mg/dL (normal 0.2), the aspartateaminotransferase level was 50 IU/L (normal 5–40), alanineaminotransferase was 60 IU/L (7–35), alkaline phosphatasewas 221 IU/L (normal 32–92), and gamma glutamyl transpep-tidase was 150 IU/L (normal 7 to 64) with albumin value of1.9 g/dL (normal 3.2 to 4.6) and INRof 1.3.The serum IgG lev-els were 22.6 g/L (normal 6.39 to 13.49). HIV 1 and 2, HBsAg,and anti-HCV were negative and an abdominal imagingrevealed the presence of only hepatosplenomegaly withoutascites or intrahepatic biliary radical dilatation and absenceof abdominal lymphadenopathy. A fundoscopy performed atthe bedside revealed features of uveitis and small retinal hem-orrhages. The imaging of the chest was within normal limits.The patient underwent a skin biopsy from the largest lesion

at the back; a percutaneous ultrasound guided liver biopsywas also done and a subsequent bone marrow study wasalso undertaken. The findings of the skin biopsy suggestedthe presence of thinned out epidermis. The dermis showedloss of adnexal structures and a rich collection of histiocytesfilled with amastigote forms of leishmaniasis (Figure 2(a)).The liver biopsy revealed the presence of acinar disarray withhepatocytes showing ballooning degeneration,mild steatosis,and glycogenated nuclei. Several foci of lobular inflammationand prominence of hyperplastic Kupffer cells were noted withformation of few small granulomas.The hyperplastic Kupffercells and granulomatous collection of macrophages showedpresence of intracellular LD bodies (Figure 2(b)) whichwas also subsequently shown in the bone marrow biopsy(Figure 3).The patient was then finally diagnosed as a case ofdisseminated mucocutaneous-cutaneous leishmaniasis withconcurrent ocular, hepatic, and simultaneous bone marrowinvolvement. She was started on antileishmanial therapywith liposomal amphotericin B at a dose of 3mg/kg bodyweight from days 1 to 10 and oral Miltefosine of 100mgper day for the next 28 days. The laboratory parameterssubsequently normalized and the patient’s visual acuity andother symptoms improved substantially during the rest ofher hospital stay. She was discharged eventually in a stablecondition, being afebrile, and is currently on regular followup.

3. Discussion

Leishmaniasis is a protozoan disease that is categorizedinto Old World disease (being prevalent in Africa, MiddleEast, Asia, and the Mediterranean) and New World disease(in areas of Central and South America). The Old Worldspecies produce, mostly, disseminated skin disease ratherthan solitary skin disease. These organisms cause cutaneous,mucocutaneous, visceral, and disseminated diseases. Cuta-neous leishmaniasis can be divided into localized, diffuse,recidivans, post kala azar dermal and mucocutaneous types.Localized form resembles lepromatous type of Hansen’sdisease with ≥10 lesions at multiple body sites.The recidivanstype resembles lupus vulgaris with psoriasiform plaques thatoccur on the face, progressing centrifugally, many monthsafter the resolution of solitary cutaneous disease. Post kala-azar dermal leishmaniasis is seen to complicate a resolved vis-ceral lesihmaniasis and finally, mucocutaneous Leishmania-sis affects both themucosal surfaces aswell as skin areas of theface, forming disfiguring lesions. The visceral leishmaniasisinvolves the visceral organs, mainly the liver and spleen andbonemarrowpresentingmostly with fever and severemalaiseassociated with pancytopenia and hypergammaglobulinemiawith pigmentation and xerosis of the skin [4]. Another vari-ety, known as the viscerotropic form, caused by the speciesLeishmania tropica (which mostly produces cutaneous formof the disease) has been described from India and Israel. Inthis form, the patient does not have the full-fledged formof visceral disease but rather has symptoms of diarrhea,malaise, and abdominal pain with loss of general well-being,with a prolonged and indolent course. The diagnosis of thisdisease relies mostly on the demonstration of the protozoan

Case Reports in Infectious Diseases 3

(a) (b) (c)

(d)

Figure 1: Clockwise, from left: nodular lesions involving the face in a disseminated pattern, mimicking lepromatous leprosy; the boggy pusdraining lesions at the back with ulceronodular features (black arrow); eye involvement in the form of nodules on the conjunctiva (yellowarrow) and conjunctival suffusion (green arrow); mucous surface involvement in the form of broken down nodular lesion on the soft palate(red arrow).

(a)

(b)

Figure 2: Histopathological examination of the liver (a) andskin lesion (b) showing features of LD bodies in the former andamastigote forms in the latter. H&E stain (400x) and eosin stain(400x), respectively.

Figure 3: Histopathological examination of the bonemarrow show-ing LD bodies within the histiocytic macrophages (black arrow);eosin stain (1000x).

in tissue samples like aspirates and biopsy samples. Imaginghas very minimal role in confirmation of Leishmaniasis.Montenegro leishmaniasis skin test and cellulose acetateelectrophoresis (for typing the protozoan species) have beenused previously.This has been replaced by the new serologicaltest, RK39, and PC R methods to detect the species ofinfecting organism [5, 6]. The simultaneous occurrence ofdifferent forms of leishmaniasis in a single host is very rare.There have been isolated case reports of concurrent forms ofleishmaniasis occurring in patients. Gontijo et al. reportedthe presence of cutaneous, visceral, and ocular leishmaniasisin a single host, postrenal transplantation [7]. Atypical formsof leishmaniasis and concurrent forms have been known tooccur in immunocompromised patients [8]. Our patient was

4 Case Reports in Infectious Diseases

immunocompetent and she has had no other comorbidities,which makes this presentation even more peculiar. Visceralleishmaniasis, traditionally, is not associated with cutaneouslesions. Ben-Ami et al. had reported the occurrence of adultvisceral leishmaniasis concurrently with a single cutaneouslesion. In their patient, they had demonstrated the presenceof Leishmania donovani complex in skin and bone marrowsamples [9]. In our patient, we could demonstrate thepresence of amastigote forms of Leishmania in the skin andliver and of LD bodies in the bone marrow with concurrentocular involvement with active fundoscopic changes. Thisspectrum of multiple organ involvement in leishmaniasishas never been reported before. Even more striking in ourpatient was that the type of cutaneous lesions seen wasof the disseminated type, closely resembling lepromatousleprosy. Hence, this concurrent occurrence of disseminatedmucocutaneous leishmaniasis, with ocular, liver, and bonemarrow involvement in a fully immunocompetent patientwould probably be the first of its kind. Mings et al. hadreported the presence of “boggy” indurated swellings in cuta-neous leishmaniasis associated with mucosal involvement[10]. This changing type of skin lesions in the course ofdisease has been noted in our patient also. Our patient hadunusual boggy, centrally sunken nodular lesions along withthe typical ulcerative and ulceronodular lesions. Schnur et al.had described unusual leishmanial strain from Israel withmultifarious characterization [11]. Faiman et al. also recentlypublished a series that shed light on the emergence of a novelcutaneous leishmaniasis pattern in Israel [12].This brings intolight the possibility of changing pattern of disease phenotypeand protozoan characteristics and eventual manifestation inthe host, for which, further work, both at the host level and atthe protozoan level, is warranted.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

References

[1] H. W. Murray, J. D. Berman, C. R. Davies, and N. G. Saravia,“Advances in leishmaniasis,”The Lancet, vol. 366, no. 9496, pp.1561–1577, 2005.

[2] M. L. Turetz, P. R. Machado, A. I. Ko et al., “Disseminated leish-maniasis: a new and emerging form of leishmaniasis observedin northeastern Brazil,” Journal of Infectious Diseases, vol. 186,no. 12, pp. 1829–1834, 2002.

[3] P. J. Guerin, P. Olliaro, S. Sundar et al., “Visceral leishmaniasis:current status of control, diagnosis, and treatment, and a pro-posed research and development agenda,”The Lancet InfectiousDiseases, vol. 2, no. 8, pp. 494–501, 2002.

[4] R. Oren, L. F. Schnur, D. Ben Yehuda, V. Mayner, E. Okon, andE.A. Rachmilewitz, “Visceral leishmaniasis: a difficult diagnosisand unusual causative agent,” Journal of Infectious Diseases, vol.164, no. 4, pp. 746–749, 1991.

[5] F. Chappuis, Y. Mueller, A. Nguimfack et al., “Diagnostic accu-racy of two rK39 antigen-based dipsticks and the formol geltest for rapid diagnosis of visceral leishmaniasis in northeastern

Uganda,” Journal of Clinical Microbiology, vol. 43, no. 12, pp.5973–5977, 2005.

[6] V. Mittal, R. Bhatia, and S. Sehgal, “Serodiagnosis of Indiankala-azar: evaluation of IFA, ELISA and CIEP tests,” Journal ofCommunicable Diseases, vol. 23, no. 2, pp. 131–134, 1991.

[7] C. M. F. Gontijo, R. S. Pacheco, F. Orefice, E. Lasmar, E. S. Silva,and M. N. Melo, “Concurrent cutaneous, visceral and ocularleishmaniasis caused by Leishmania (Viannia) braziliensis in akidney transplant patient,”Memorias do InstitutoOswaldo Cruz,vol. 97, no. 5, pp. 751–753, 2002.

[8] S. Marques, F. Aldomiro, A. C. Camoes et al., “Simultaneousvisceral and cutaneous Leishmaniasis in HIV infected patients,”in Proceedings of the 14th International AIDS Conference, 2002,abstract no. B10266.

[9] R. Ben-Ami, L. F. Schnur, Y. Golan, C. L. Jaffe, T. Mardi, and D.Zeltser, “Cutaneous involvement in a rare case of adult visceralleishmaniasis acquired in Israel,” Journal of Infection, vol. 44, no.3, pp. 181–184, 2002.

[10] S. Mings, J. C. Beck, C. Davidson, A. L. Ondo, S. D. Shanler, andJ. Berman, “Cutaneous leishmaniasis with boggy indurationand simultaneous mucosal disease,” The American Journal ofTropical Medicine and Hygiene, vol. 80, no. 1, pp. 3–5, 2009.

[11] L. F. Schnur, S. E. O. Meredith, D. H. Beach, and A. Smyth,“Multifarious characterization of an unusual leishmanial strainfrom Israel,” Annals of Tropical Medicine and Parasitology, vol.89, p. 107, 1995.

[12] R. Faiman, I. Abbasi, C. Jaffe et al., “A newly emerged cutaneousleishmaniasis focus in northern Israel and two new reservoirhosts of Leishmania major,” PLoS Neglected Tropical Diseases,vol. 7, no. 2, article e20, 2013.

Submit your manuscripts athttp://www.hindawi.com

Stem CellsInternational

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinson’s Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

Documents

Case Report Simultaneous Occurrence of Ocular ...downloads.hindawi.com/journals/criid/2014/837625.pdfDisseminated Mucocutaneous, and Multivisceral Involvement of Leishmaniasis